The short extracellular domain of the T cell receptor zeta chain is involved in assembly and signal transduction.
The zeta chain is required in the TCR complex to guarantee its surface expression and function. However, an understanding of the interaction(s) between the zeta chain and the other proteins in the TCR/CD3 has not yet been achieved. In this report, we attempt to assign a functional role to the short extracellular (EC) domain of the zeta chain by studying its unique positive charge, a lysine at position 9, because of its interesting location to the interchain disulphide bond of the zeta chain homodimer. We show that amino acid exchanges of lysine 9 to glycine, serine, cysteine or asparagine generate TCR complexes which are clearly defective in antigenic signalling. Interestingly, the non-conservative point mutations were segregating TCR complex signalling pathways. However, lysine 9 is not critical for TCR complex surface expression unless the positively charged lysine is exchanged for the negatively charged amino acid aspartic acid. The zeta chain mutant bearing a lysine to cysteine exchange is the sole mutant to be inefficiently co-precipitated with the TCR/CD3 complex suggesting a loose interaction of the zeta chain within the TCR complex.
Bolliger
L
L
Basel Institute for Immunology, Switzerland. Luca.Bolliger@bii.ch
Johansson
B
B
Palmer
E
E
D000595:Amino Acid Sequence; D001665:Binding Sites; D017252:CD3 Complex / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D015398:Signal Transduction; D013499:Surface Properties; D014407:Tumor Cells, Cultured
D017252:CD3 Complex; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; C054979:antigen T cell receptor, zeta chain